Evidence map›Paper›PMID 34794463›Full record

ArticleVirology journal2021

Serotype-dependent recombinant adeno-associated vector (AAV) infection of Epstein-Barr virus-positive B-cells, towards recombinant AAV-based therapy of focal EBV + lymphoproliferative disorders.

Elham Ahmadi, Mehrdad Ravanshad, Jun Xie, Rajesh Panigrahi, Sandeep S Jubbal, Santosh Kumar Guru, Gao Guangping, Mazyar Ziyaeyan, Joyce Fingeroth

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Virology journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Viral Vector-Based Gene Therapy.International journal of molecular sciences · 2023
    Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Elham AhmadiDepartment of Virology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-331, Tehran, Iran.
Mehrdad RavanshadDepartment of Virology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-331, Tehran, Iran. ravanshad@modares.ac.ir.
Jun XieHorae Gene Therapy Center, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Rajesh PanigrahiDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Sandeep S JubbalDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Santosh Kumar GuruDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Gao GuangpingHorae Gene Therapy Center, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Mazyar ZiyaeyanAlborzi Clinical Microbiology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Joyce FingerothDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA. joyce.fingeroth@umassmed.edu.ORCID 0000-0003-1620-1731
University of Massachusetts Chan Medical School · USTarbiat Modares University · IRShiraz University of Medical Sciences · IR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundB-cell proliferative disorders, such as post-transplant lymphoproliferative disease (PTLD), are increased among persons afflicted by T-cell compromise. Most are Epstein-Barr virus (EBV) + and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy, immunotherapy and radiation therapy by reducing systemic toxicity. Despite extensive study as a vehicle for gene therapy, adeno-associated viruses (AAV) have rarely been applied to human cancer research due to technical and theoretical obstacles. Moreover, human B-cells have historically been described as resistant to AAV infection. Nonetheless, advances using different recombinant (r)AAV serotypes with unique tropisms to deliver cytotoxic therapy suggested a localized anti-tumor approach was feasible.

methodsAs a prelude to the development of a therapeutic vehicle, the ability of fifteen distinct EGFP-bearing rAAV serotypes to transduce human B-cells, including primary, immortalized, and B-cell tumor lines ± EBV was assessed by confocal microscopy, flow cytometry and subsequently cell viability assay.

resultsRank order analysis revealed augmented transduction by rAAV6.2 and closely related virions. EBV infection of EBV-negative B-cell tumor lines and EBV immortalization of primary B-cells increased susceptibility to rAAV6.2 transduction. As a proof of concept, transduction by rAAV6.2 encoding herpes simplex virus type 1 (HSV1)-thymidine kinase (TK) eliminated TK-negative rhabdomyosarcoma cells and diminished viability of transduced B-cell lines upon incubation with ganciclovir.

conclusionsrAAV serotypes differentially transduce human B-cell lines reversing the dogma that human B-cells are refractory to AAV infection. EBV + B-cells display increased susceptibility to rAAV6.2 infection, uncovering a new method for improved nucleic acid transfer into transfection-resistant B-cell lines. The introduction of a functional suicide gene into the rAAV6.2 genome identifies a candidate vector for the development of rAAV-based oncolytic therapy targeting focal EBV-bearing B-lymphoproliferative disorders.

Indexed as

Epstein-Barr Virus InfectionsLymphoproliferative DisordersDependovirusHerpesvirus 4, HumanHumansSerogroupB-cellsEBVFocal tumorsMononucleosisPTLDrAAVSuicide geneTransfection

Identifiers

PMID34794463
PMCPMC8600692
OpenAlexW3211360068

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.